HUMAN IMMUNOLOGY CENTERS OF EXCELLENCE
Release Date: March 6, 1998
RFA: AI-98-001
P.T.
National Institute of Allergy and Infectious Diseases
Letter of Intent Receipt Date: August 23, 1998
Application Receipt Date: October 23, 1998
APPLICATIONS IN RESPONSE TO THIS REQUEST FOR APPLICATIONS (RFA) MUST BE PREPARED
USING A MULTI-PROJECT GRANT APPLICATION FORMAT; SPECIFIC INSTRUCTIONS FOR
COMPLETING THE APPLICATION ARE IN AN NIAID BROCHURE ENTITLED "INSTRUCTIONS FOR
APPLICATIONS FOR MULTI-PROJECT AWARDS.þ
PURPOSE
The National Institute of Allergy and Infectious Diseases (NIAID), National
Institutes of Health (NIH), invites applications for program project grants to
support interactive, synergistic studies on the basic mechanisms that regulate
human immune responses. Of primary interest are multidisciplinary research
programs focused on defining clinically relevant genetic, biochemical, cellular
and systemic parameters of human immunity and tolerance. Studies should strive
to identify basic principles of immune regulation and to facilitate the
translation of knowledge from animal studies into clinical approaches for the
prevention and treatment of human diseases such as autoimmunity, allergy,
infections, transplant rejection and inflammatory diseases.
HEALTHY PEOPLE 2000
The Public Health Service (PHS) is committed to achieving the health promotion
and disease prevention objectives of "Healthy People 2000," a PHS-led national
activity for setting priority areas. This RFA, Human Immunology Centers of
Excellence, is related to the priority area of immunization and infectious
diseases. Potential applicants may obtain a copy of "Healthy People 2000" (Full
Report: Stock No. 017-001-00474-0 or Summary Report: Stock No. 017-001-00473-1)
through the Superintendent of Documents, Government Printing Office, Washington,
DC 20402-9325 (telephone 202-512-1800).
ELIGIBILITY REQUIREMENTS
Research grant applications may be submitted by domestic for-profit and non-
profit organizations, public and private institutions, such as universities,
colleges, hospitals, laboratories, units of State and local governments, and
eligible agencies of the Federal government. Foreign organizations are not
eligible to apply. Racial/ethnic minority individuals, women, and persons with
disabilities are encouraged to apply as Principal Investigators.
MECHANISM OF SUPPORT
The mechanism of support will be the program project (P01) grant. This type of
award supports broadly based multidisciplinary research programs that have a
well-defined central research focus or objective. An important feature is that
the interrelationships among the individual scientifically meritorious projects
will result in a greater contribution to the overall program goals than if each
project was pursued individually. The program project grant consists of a
minimum of three interrelated individual research projects that contribute to the
program objective. The award also can provide support for certain common
resources termed cores. Such resources should be utilized by two or more
projects within the award.
Responsibility for the planning, direction, and execution of the proposed
projects will be solely that of the applicant. The total project period may not
exceed five years. At this time, the NIAID is administratively limiting the
duration of P01 grants to four years; this administrative limitation may change
in the future. The earliest anticipated award date is August, 1999.
FUNDS AVAILABLE
The estimated total funds (direct and indirect) available for the first year of
support for this RFA will $3.0 million. In fiscal year 1999, the NIAID plans to
make approximately 4 awards related to this RFA. This level of support is
dependent on the receipt of a sufficient number of applications of high
scientific merit. Applications requesting budgets in excess of $750,000 in total
(direct and indirect) first-year costs must obtain approval from the Program
contact listed in þINQUIRIESþ prior to submission. The usual PHS policies
governing grants administration and management will apply. Although this program
is provided for in the financial plans of the NIAID, awards pursuant to this RFA
are contingent upon the availability of funds for this purpose. Funding beyond
the first and subsequent years of the grant will be contingent upon satisfactory
progress during the preceding years and availability of funds. At this time, the
NIAID has not determined whether or how this solicitation will be continued
beyond the present RFA.
RESEARCH OBJECTIVES
Background
Considerable progress in understanding the basic mechanisms of immune regulation
has occurred in recent years, but comprehensive analyses of normal and pathogenic
immune responses have been conducted primarily in non-human animal model systems.
Many aspects of human immunology are still poorly defined and pathways that are
important in animal systems might not represent optimal therapeutic targets in
man. Infectious and immune-mediated diseases currently impose enormous economic
and social costs, and a more complete understanding of the human immune system
and the ways in which it can be safely modified will greatly facilitate the
development of new clinical applications.
Human studies are limited by a more restricted set of experimental protocols than
can be performed in animals. Extensive genetic heterogeneity and environmental
variations further increase the difficulty of obtaining detailed information
about the complex processes that govern immune responses in vivo. However,
current experimental approaches allow for the detection and quantitation of an
increasing number of immunological parameters that correlate with human disease
pathogenesis and outcomes. Advances in molecular biology, for example, have
provided mechanistic explanations for diseases of abnormal cell development, such
as lymphoproliferative disorders and immunodeficiency diseases. Enhanced
techniques for HLA typing and gene sequencing have generated new paradigms for
understanding transplant rejection and disease susceptibility, and the ability
to produce recombinant cytokines and humanized antibodies provides promising new
immunomodulatory agents for therapy. Rapid advances in determining the three-
dimensional structures of proteins that regulate the immune system also provide
new opportunities for innovative drug development for both infectious and immune-
mediated diseases. Furthermore, the extraordinary accomplishments of the human
genome project will soon result in an unprecedented wealth of genetic
information, thus facilitating advances in defining the biochemical basis for
human immune functions, and in identifying novel cellular and molecular targets
for vaccine development and immune intervention.
Research Objectives and Scope
The goal of this RFA is to support highly integrated, multidisciplinary research
programs focused on defining the mechanisms responsible for normal or pathogenic
human immune responses. Innovative and definitive approaches to the study of
human immune regulation are of particular interest. Projects that incorporate
clinically relevant animal models into a complementary framework of human studies
that are also included in the program are acceptable. In addition, relevant
clinical studies in humans are within the scope of this RFA. Research topics of
interest include, but are not limited to, the following:
o identification of the types of human immune responses, such as dominant CTL,
NK, specific cytokine or antibody isotype responses, that are critical for
protection from, or reversal of, specific disease states (autoimmunity, allergy,
transplant rejection, infectious diseases);
o novel, minimally invasive experimental approaches that move beyond PBL assays
in order to identify mechanisms of human immune regulation or to monitor antigen-
specific immune responses;
o identification of the most effective antigen delivery systems for the induction
of immunity or tolerance;
o characterization of the mechanisms responsible for differential regulation of
immune responses in children, adults and the elderly;
o definition of ontogeny of the human immune system and identification of
essential parameters for reconstitution of deficient or ablated immunity;
o identification of molecular targets applicable to the development of novel
adjuvants and vaccines for human use;
o characterization of molecular mechanisms responsible for human T and B memory
cell generation and maintenance;
o immunoregulation by cytokines and their receptors; and
o genetic control of immune responsiveness and immune effector mechanisms.
INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS
It is the policy of the NIH that women and members of minority groups and their
subpopulations must be included in all NIH supported biomedical and behavioral
research projects involving human subjects, unless a clear and compelling
rationale and justification are provided that inclusion is inappropriate with
respect to the health of the subjects of the purpose of the research. This
policy results from the NIH Revitalization Act of 1993 (Section 492B of Public
Law 103-43).
All investigators proposing research involving human subjects should read the
"NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical
Research", which have been published in the Federal Register of March 28, 1994
(FR 59 14508-14513) and the NIH Guide for Grants and Contracts, Vol. 23, No. 11,
March 18, 1994.
Investigators may obtain copies from these sources or from Dr. Helen Quill
(listed in INQUIRIES below) who may also provide additional relevant information
concerning the policy.
LETTER OF INTENT
Prospective applicants are asked to submit, by August 23, 1998, a letter of
intent that includes a descriptive title of the overall proposed research, the
name, address and telephone number of the Principal Investigator, and the number
and title of this RFA. Although the letter of intent is not required, is not
binding, does not commit the sender to submit an application, and does not enter
into the review of subsequent applications, the information that it contains
allows NIAID staff to estimate the potential review workload and to avoid
conflict of interest in the review. The letter of intent is to be sent to Dr.
Kevin Callahan at the address listed under INQUIRIES.
APPLICATION PROCEDURES
Applicants for P01 grants must follow special application guidelines in the
NIAID Brochure entitled INSTRUCTIONS FOR APPLICATIONS FOR MULTI-PROJECT AWARDS
(September 1997); this brochure is available from NIAID staff listed in
INQUIRIES and via the WWW at: http://www.niaid.nih.gov/ncn/grants/
multibron.htm
Applications are to be submitted on the standard research grant application form
PHS 398 (rev. 5/95). Application kits are available at most institutional
offices of sponsored research and may be obtained from the Division of Extramural
Outreach and Information, National Institutes of Health, 6701 Rockledge Drive,
MSC 7910, Bethesda, MD 20892-7910, telephone (301) 435-0714, email:
asknih@od.nih.gov.
For purposes of identification and processing, item 2 on the face page of the
application must be marked "YES" and the RFA number "AI-98-001" and the words
"Human Immunology Centers of Excellence" must be typed in.
Applications must be received by October 23, 1998. Applications that are not
received as a single package on the receipt date or that do not conform to the
instructions contained in PHS 398 (rev. 5/95) Application Kit (as modified in,
and superseded by, the NIAID BROCHURE ENTITLED "INSTRUCTIONS FOR APPLICATIONS FOR
MULTI-PROJECT AWARDS"), will be judged non-responsive and will be returned to the
applicant. The RFA label available in the application form PHS 398 must be
affixed to the bottom of the face page. Failure to use this label could result
in delayed processing of the application such that it may not reach the review
committee in time for review.
Applicants from institutions that have a General Clinical Research Center (GCRC)
funded by the NIH National Center for Research Resources may wish to identify the
GCRC as a resource for conducting the proposed research. If so, a letter of
agreement from either the GCRC program director or principal investigator should
be included with the application.
It is highly recommended that the appropriate NIAID program contact be consulted
before submitting the letter of intent and during the early stages of preparation
of the application. (See program contact under INQUIRIES).
Submit a signed, typewritten original of the application, including the
checklist, and three signed, exact, single-sided photocopies, in one package to:
CENTER FOR SCIENTIFIC REVIEW
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710
BETHESDA, MD 20892-7710
BETHESDA, MD 20817 (for express/courier service)
At the time of submission, two additional exact copies of the grant application
and all five sets of any appendix material must be sent to Dr. Kevin Callahan at
the address listed under INQUIRIES.
Concurrent submission of an R01 and a Component Project of a Multi-project
Application: NIH policy permits a component research project of a multi-project
grant application to be concurrently submitted as a traditional individual
research project (R01) application. If, following review, both the multi-project
application and the R01 application are found to be in the fundable range, the
investigator must relinquish the R01 and will not have the option to withdraw
from the multi-project grant. This is an NIH policy intended to preserve the
scientific integrity of a multi-project grant, which may be seriously compromised
if a strong component project(s) is removed from the program. Investigators
wishing to participate in a multi-project grant must be aware of this policy
before making a commitment to the Principal Investigator and awarding
institution.
SPECIAL INSTRUCTIONS FOR COMPLETION OF APPLICATIONS IN RESPONSE TO THIS RFA
Applicants for P01 grants must follow special application guidelines in the NIAID
Brochure entitled INSTRUCTIONS FOR APPLICATIONS FOR MULTI-PROJECT AWARDS
(September 1997); this brochure is available via the WWW at:
http://www.niaid.nih.gov/ncn/grants/multibron.htm.
The brochure presents specific instructions for sections of the PHS 398 (rev.
5/95) application form that should be completed differently than usual. For all
other items in the application, follow the usual instructions on pages 5-20 of
the PHS 398 booklet.
REVIEW CONSIDERATIONS
Review Procedures
Upon receipt, applications will be reviewed for completeness by the NIH Center
for Scientific Review and for responsiveness by NIAID staff. Incomplete and/or
non-responsive applications will be returned to the applicant without further
consideration.
Applications that are complete and responsive to the RFA will be evaluated for
scientific and technical merit by an appropriate peer review group convened by
the NIAID in accordance with the review criteria stated below. As part of the
initial merit review, a process may be used by the initial review group in which
applications will be determined to be competitive or non-competitive based on
their scientific merit relative to other applications received in response to the
RFA.
Applications judged to be competitive will be discussed and be assigned a
priority score. Applications determined to be non-competitive will be withdrawn
from further consideration and the Principal Investigator and the official
signing for the applicant organization will be notified. The second level of
review will be provided by the National Advisory Allergy and Infectious Diseases
Council.
Review Criteria
The general criteria for P01 grant applications are presented in the NIAID
brochure entitled INSTRUCTIONS FOR APPLICATIONS FOR MULTI-PROJECT AWARDS
(September 1997).
AWARD CRITERIA
Funding decisions will be made on the basis of scientific and technical merit as
determined by peer review, program balance, and the availability of funds.
INQUIRIES
Written and telephone inquiries concerning this RFA are encouraged. The
opportunity to clarify any issues or questions from potential applicants is
welcome.
Requests for the NIAID brochure "INSTRUCTIONS FOR APPLICATIONS FOR MULTI-PROJECT
AWARDS" as well as inquiries regarding programmatic (eligibility and research
scope) issues, may be directed to:
Helen Quill, Ph.D.
Division of Allergy, Immunology and Transplantation
National Institute of Allergy and Infectious Diseases
6003 Executive Boulevard, Room 4A22
Bethesda, MD 20892-7640
Telephone: (301) 496-7551
FAX: (301) 402-2571
Email: Helen_Quill@nih.gov
Direct inquiries regarding preparation of the application and review issues, and
address the letter of intent to, and mail two copies of the application and all
five sets of appendices to:
Kevin Callahan, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
6003 Executive Boulevard, Room 4C-20
Bethesda, MD 20892-7610
Telephone: (301)496-2550
Email: kc92t@nih.gov
Direct inquiries regarding fiscal matters to:
Pam Fleming
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
6003 Executive Boulevard, Room 4C-25
Bethesda, MD 20892-7610
Telephone: (301) 496-7075
FAX: (301) 480-3780
Email: pf49e@nih.gov
Schedule
Letter of Intent Receipt Date: August 23, 1998
Application Receipt Date: October 23, 1998
Scientific Review Date: February 1999
Advisory Council Date: May 1999
Earliest Date of Award: August 1999
AUTHORITY AND REGULATIONS
This program is supported under authorization of the Public Health Service Act,
Sec. 301 (c), Public Law 78-410, as amended. The Catalogue of Federal Domestic
Assistance Citation is No. 93.855 - Immunology, Allergy, and Transplantation
Research. Awards will be administered under PHS grants policies and Federal
Regulations 42 CFR Part 52 and 45 CFR Part 74. This program is not subject to
the intergovernmental review requirements of Executive Order 12372 or Health
Systems review.
The PHS strongly encourages all grant and contract recipients to provide a smoke-
free workplace and promote the non-use of all tobacco products. In addition,
Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain
facilities (or in some cases, any portion of a facility) in which regular or
routine education, library, day care, health care or early childhood development
services are provided to children. This is consistent with the PHS mission to
protect and advance the physical and mental health of the American people.